Current Practices in Prescribing Auto-Injectable Epinephrine during Immunotherapy amongst Otolaryngic Allergists

Purpose: Allergen immunotherapy (AIT) while usually safe, is not without risk. Both sublingual (SLIT) and subcutaneous immunotherapy (SCIT) have the potential for systemic reactions including anaphylaxis. Materials and Methods: A short survey was distributed to fellows of the American Academy of Otolaryngic Allergy (AAOA) (n = 553) in July of 2019 to determine current prescribing practices. Results: A total of 103/553 surveys were completed, giving a response rate of 18.6%. Prescribing patterns for SCIT showed 79.6% prescribed auto-injectable epinephrine (AIE) to all patients, 11.7% prescribed only to high risk patients, while 1.9% did not prescribe AIE at all. SLIT showed similar patterns with 71.8% prescribing AIE to all, 11.7% to high risk or letting patient choose, and 6.8% did not prescribe to anyone. Just under half of the physicians responded affirmatively to giving a written anaphylaxis plan to patients on immunotherapy. 48.5% physicians reported treating in-office anaphylaxis due to SCIT or skin testing in the past year, while 6% reported anaphylaxis due to SLIT. Conclusions: A majority of otolaryngic allergists are still prescribing AIE for both SCIT and SLIT. With the recent higher costs attributed to AIE as well as drug shortages, some physicians are risk-stratifying patients. While SCIT has a higher risk for treatment related systemic reactions, anaphylaxis does occur with SLIT, thus making it imperative to counsel patients on a clear anaphylaxis protocol in all forms of AIT.

Epinephrine also acts on beta cells and insulin secretion

In a recent review examining neurotransmitter modulation of insulin secretion,the significant impact of epinephrine was not addressed.Its primary action involves inhibiting insulin release via alpha-adrenergic receptors,thereby reducing the response to insulin secretion stimulators,through the activation of K+channels and resulting in membrane hyperpolarization in beta cells.

Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

Analysis of the Effects of Local Injection of Epinephrine and Lidocaine on Postoperative Pain and Bleeding in Children Undergoing Tonsillectomy

Objective:To explore the effects of local injection of epinephrine and lidocaine on postoperative pain and bleeding in children undergoing tonsillectomy.Methods:Sixty-eight children who underwent a tonsillectomy in our hospital from March 2019 to October 2020 were selected.The children were randomly divided into two groups of 34 cases each.The observation group received local anesthetic injections of lidocaine and the control group received local anesthetic injections of epinephrine.The postoperative pain,operation time,blood pressure changes,and intraoperative blood loss of the two groups of children were observed and analyzed.Results:The postoperative pain,operation time,and intraoperative blood loss scores of the children in the observation group were 4.36±0.69,0.36±0.09,and 39.36±1.78 respectively,which were significantly better than those of the children in the control group(P<0.05)at 5.36±0.77,0.79±0.05,and 45.36±1.56,respectively.The systolic blood pressure and diastolic blood pressure of the observation group 3 minutes before surgery and 180 minutes after surgery were no different from those of the control group(P>0.05).Conclusion:Local injection of epinephrine and lidocaine effectively relieved postoperative pain and reduced bleeding in children undergoing tonsillectomy as compared to epinephrine alone.

Predictors of rebleeding after initial hemostasis with epinephrine injection in high-risk ulcers

AIM: To identify the predictors of rebleeding after initial hemostasis with epinephrine injection (EI) in patients with high-risk ulcers. METHODS: Recent studies have revealed that endoscopic thermocoagulation, or clips alone or combined with EI are superior to EI alone to arrest ulcer bleeding. However, the reality is that EI monotherapy is still common in clinical practice. From October 2006 to April 2008, high-risk ulcer patients in whom hemorrhage was stopped after EI monotherapy were studied using clinical, laboratory and endoscopic variables. The patients were divided into 2 groups: sustained hemostasis and rebleeding. RESULTS: A total of 175 patients (144, sustainedhemostasis; 31, rebleeding) were enrolled. Univariate analysis revealed that older age (≥ 60 years), advanced American Society of Anesthesiology (ASA) status (category Ⅲ , Ⅳ and Ⅴ ), shock, severe anemia (hemoglobin < 80 g/L), EI dose ≥ 12 mL and severe bleeding signs (SBS) including hematemesis or hematochezia were the factors which predicted rebleeding. However, only older age, severe anemia, high EI dose and SBS were independent predictors. Among 31 rebleeding patients, 10 (32.2%) underwent surgical hemostasis, 15 (48.4%) suffered from delayed hemostasis causing major complications and 13 (41.9%) died of these complications. CONCLUSION: Endoscopic EI monotherapy in patients with high-risk ulcers should be avoided. Initial hemostasis with thermocoagulation, clips or additional hemostasis after EI is mandatory for such patients to ensure better hemostatic status and to prevent subsequent rebleeding, surgery, morbidity and mortality.

Electroanalysis and simultaneous determination of dopamine and epinephrine at poly(isonicotinic acid)-modified carbon paste electrode in the presence of ascorbic acid

A carbon paste electrode modified with electropolymerized fills of isonicotinic acid was developed. The modified electrode shows excellent electrocatalytic activity toward the oxidation of both dopamine （DA） and epinephrine （EP）. Separation of the reduction peak potentials for dopamine and epinephrine was about 357 mV in pH 5.3 phosphate buffer solution （PBS） and the character was used for the detection DA and EP simultaneously. The peak currents increase linearly with DA and EP concentration over the range of 8.0×10^-5 to 7.0×10^-4 mol/L and 5.0×10^-6 to 1.0×10^-4 mol/L with detection limits of 2×10^-5 and 1×10^-6 mol/L, respectively. The interference studies showed that the modified electrode exhibits excellent selectivity in the presence of large excess of ascorbic acid （AA）.

Optimal injection volume of epinephrine for endoscopic treatment of peptic ulcer bleedinq

AIM： To define the optimal injection volume of epinephrine with high efficacy for hemostasis and low complication rate in patients with actively bleeding ulcers. METHODS： This prospective, randomized, comparative trial was conducted in a medical center. A total of 228 patients with actively bleeding ulcers （spurting or oozing） were randomly assigned to three groups with 20, 30 and 40 mL endoscopic injections of an 1：10000 solution of epinephrine. The hemostatic effects and clinical outcomes were compared between the three groups. RESULTS： There were no significant differences in all background variables between the three groups. Initial hemostasis was achieved in 97.4%, 98.7% and 100% of patients respectively in the 20, 30 and 40 mL epinephrine groups. There were no significant differences in the rate of initial hemostasis between the three groups. The rate of peptic ulcer perforation was significantly higher in the 40 mL epinephrine group than in the 20 and 30 mL epinephrine groups （P 〈 0.05）. The rate of recurrent bleeding was significantly higher in the 20 mL epinephrine group （20.3%） than in the 30 （5.3%） and 40 mL （2.8 %） epinephrine groups （P 〈 0.01）. There were no significant differences in the rates of surgical intervention, the amount of transfusion requirements, the days of hospitalization, the deaths from bleeding and 30 d mortality between the three groups. The number of patients who developed epigastric pain due to endoscopic injection, was significantly higher in the 40 mL epinephrine group （51/76） than in the 20 （2/76） and 30 mL （5/76） epinephrine groups （P 〈 0.001）. Significant elevation of systolic blood pressure after endoscopic injection was observed in the 40 mL epinephrine group （P 〈 0.01）. Significant decreasing and normalization of pulse rates after endoscopic injections were observed in the 20 mL and 30 mL epinephrine groups （P 〈 0.01）.CONCLUSION： Injection of 30 mL diluted epinephrine （1：10000） can effectively prevent recurrent bleeding with a low rate of complications. The optimal injection volume of epinephrine for endoscopic treatment of an actively bleeding ulcer （spurting or oozing） is 30 mL.

Epinephrine injection therapy versus a combination of epinepnrine injection and endoscopic hemoclip in the treatment of bleeding ulcers

AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combination therapy and those treated with epinephrine injection alone.METHODS: A total of 293 patients (211 males, 82females) underwent endoscopic therapy for bleeding peptic ulcers. Of these, 202 patients (152 males, 50females) received epinephrine injection therapy while 91patients (59 males, 32 females) received combination therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic rates, rebleeding rates, need for emergency surgery and 30-d mortality were the outcome measures studied.RESULTS: Patients who received combination therapy were significantly older (mean age 66±16 years, range24-90 years) and more suffered from chronic renal failure compared to those who received epinephrine injection therapy alone (mean age 61±17 years, range 21-89 years).Failure to achieve permanent hemostasis was 4% in the group who received epinephrine injection alone and 11%in the group who received combination therapy. When the differences in age and renal function between the two treatment groups were taken into account by multivariate analysis, the rates of initial hemostasis,rebleeding rates, need for surgery and 30-d mortality for both treatment options were not significantly different.CONCLUSION: Combination therapy of epinephrine injection with endoscopic hemoclip application is an effective method of achieving hemostasis in bleeding peptic ulcer diseases. However, superiority of combination therapy over epinephrine injection alone, could not be demonstrated.

Comparison of postpolypectomy bleeding between epinephrine and saline submucosal injection for large colon polyps by conventional polypectomy:A prospective randomized,multicenter study

AIM:To evaluate and compare the clinical outcomes of prophylactic submucosal saline-epinephrine injection and saline injection alone for large colon polyps by conventional polypectomy. METHODS:A prospective study was conducted from July 2003 to July 2004 at 11 tertiary endoscopic centers. Large colon polyps (> 10 mm in diameter) wererandomized to undergo endoscopic polypectomy with submucosal saline-epinephrine injection (epinephrine group) or normal saline injection (saline group). Endoscopic polypectomy was performed by the conventional snare method,and early (< 12 h) and late bleeding complications (12 h-30 d) were observed. RESULTS:A total of 561 polyps in 486 patients were resected by endoscopic polypectomy. Overall,bleeding complications occurred in 7.6% (37/486) of the patients,including 4.9% (12/244) in the epinephrine group,and 10.3% (25/242) in the saline group. Early and late postpolypectomy bleeding (PPB) occurred in 6.6% (32/486) and 1% (5/486) of the patients,respectively,including 4.5% (11/244),0.4% (1/244) in the epinephrine group,and 8.7% (21/242),1.7% (4/242) in the saline group. No significant differences in the rates of overall,early and late PPB were observed between the 2 groups. Multivariate stepwise logistic regression analysis revealed that large size (> 2 cm) and neoplastic polyps were independently and significantly associated with the presence of PPB. CONCLUSION:The prophylactic submucosal injection of diluted epinephrine does not appear to provide an additional advantage over the saline injection alone for the prevention of PPB.

Low doses of intravenous epinephrine for refractory sustained monomorphic ventricular tachycardia

We report three cases of sustained monomorphic ventricular tachycardia(VT) in the setting of coronary artery disease,resistant to beta-blockers in two patients and to amiodarone in all,successfully terminated by low doses of intravenous(IV) epinephrine.VT was the first manifestation of coronary artery disease in one patient,whereas the other two patients had a previous history of myocardial infarction and were recipients of an implantable cardioverter-defibrillator(ICD).One of these two patients experienced an arrhythmic storm.All had hemodynamic instability at the time of epinephrine administration.A single slow administration of IV epinephrine(0.5 to 1 mg administered over 30 to 60 s) restored sinus rhythm after 30-90 s with only minor side effects.In the ICD patient with recurrent VT and several cardioversions due to transformation of VT to ventricular fibrillation,epinephrine injection led to the avoidance of further shocks.Although potentially harmful,low doses of IV epinephrine used alone or in combination with beta-blocker treatment and electrical cardioversion may be an alternative effective therapy for sustained monomorphic VT refractory to amiodarone.The role of epinephrine in the termination of VT should be studied further,especially in patients pre-treated with amiodarone in combination with beta-blockers.

Safety of epinephrine for anaphylaxis in the emergency setting

BACKGROUND:While epinephrine is the recommended first-line therapy for the reversal of anaphylaxis symptoms,inappropriate use persists because of misunderstandings about proper dosing and administration or misconceptions about its safety.The objective of this review was to evaluate the safety of epinephrine for patients with anaphylaxis,including other emergent conditions,treated in emergency care settings.METHODS:A MEDLINE search using PubMed was conducted to identify articles that discuss the dosing,administration,and safety of epinephrine in the emergency setting for anaphylaxis and other conditions.RESULTS:Epinephrine is safe for anaphylaxis when given at the correct dose by intramuscular injection.The majority of dosing errors and cardiovascular adverse reactions occur when epinephrine is given intravenously or incorrectly dosed.CONCLUSION:Epinephrine by intramuscular injection is a safe therapy for anaphylaxis but training may still be necessary in emergency care settings to minimize drug dosing and administration errors and to allay concerns about its safety.

Treating delayed endoscopic sphincterotomy-induced bleeding:Epinephrine injection with or without thermotherapy

AIM： To compare the hemostatic efficacy between epinephrine injection alone and epinephrine injection combined with thermotherapy for delayed postendoscopic sphincterotomy （ES） bleeding. METHODS： Cases with delayed post-ES bleeding undergoing epinephrine injection alone （epinephrine injection group, n = 26） or epinephrine combined with thermotherapy （combination therapy group, n = 33） in our institution between 1999 and 2007 were retrospectively investigated. The main outcome measurements were： initial endoscopic hemostasis, rebleeding, complications, requirement of angiographic embolization or surgery, requirement for blood transfusion, and mortality. RESULTS： The initial hemostatic efficacy was 96.2% for epinephrine injection alone and 100% for combination therapy （P = 0.44）. There were four patients with re-bleeding in each group （16.0% vs 12.1%, P = 0.72）. There was only one complication of pancreatitis from the combination therapy group. Three patients （11.5%） in the epinephrine injection group and one patient （3%） in the combination therapy group required angiographic embolization or surgery （P = 0.31）. The total number of blood transfusions was not significantly different between the two groups （3.5 ± 4.6 U vs 3.5 ± 4.5 U, P = 0.94）. There was no bleeding-related death in either group. CONCLUSION： Epinephrine injection alone is as effective as epinephrine injection combined with thermotherapy for the management of delayed post- ES bleeding.

Intercalation of Epinephrine with Calf-thymus ds-DNA

A strong interaction between double stranded calf-thymus DNA (ds-DNA) and epinephrine but no interaction between single stranded calf-thymus DNA (ss-DNA) and epinephrine were observed by the use of UV-spectroscopy and cyclic voltammetry. It is suggested that the interaction leads to an intercalation of EP molecules into the groove of ds-DNA and the formation of ds-DNA(EP)(n) complex.

2,3-Dimercaptosuccinic acid self-assembled gold electrode for the simultaneous determination of epinephrine and dopamine

Simultaneous determination of epinephrine （EP） and dopamine （DA） at 2,3-dimercaptosuccinic acid （DMSA） modified electrode was studied. The oxidation peaks of the mixture of EP and DA appeared at the same potential, but the cathodic peak currents were only linear to the concentration of DA, whereas the anodic peak currents were equal to the sum of individual anodic peak currents of EP and DA. Therefore, a novel electrochemical method for the simultaneous determination of EP and DA at a DMSA modified electrode （DMSA/Au electrode） by cyclic voltammetry was established. The DMSA self-assembled electrode showed good sensitivity, selectivity and stability and could be used to determine DA and EP, simultaneously, in the real application with satisfactory results.

Enantiomeric Separation of Epinephrine and Salbutamol by Micellar Electrokinetic Chromatography Using β-Cyclodextrin as Chiral Additive

Enantiomeric separation of epinephrine and salbutamol was investigated by micellar electrokinetic chromatography employing β-cyclodextrin as chiral additive in ammonium chloride-ammonia solution. The analytes were detected by electrochemistry using gold microelectrode at +0.65 V versus SCE reference electrode. The effects of detection potential, concentration of β-cyclodextrin, concentration of sodium dodecyl sulfate, pH value of electrolyte and applied voltage were discussed.

Cyclic Voltammetry Determination of Epinephrine with a Nano-gold Modified Glassy Carbon Electrode in the Presence of High Concentration Ascorbic Acid

Nano-gold (NG) modified glassy carbon electrodes (GCEs) were used for determination of epinephrine (EP) in the presence of high concentration ascorbic acid (AA) by cyclic voltammetry (CV). This modified electrode can not only catalytically oxidize EP and AA, but also separate the catalytic peak potentials of EP and AA by about 183.5 mV. In pH = 7.0 ogisogate byffer solution, the linear range of epinephrine was 5 106 ~ 1 ?10-4 mol/L.

Effects of epinephrine on angiogenesis-related gene expressions in cultured rat cardiomyocytes

Epinephrine is often used for the treatment of patients with heart failure, low cardiac output and cardiac arrest. It can acutely improve hemodynamic parameters; however, it does not seem to improve longer term clinical outcomes. Therefore, we hypothesized that epinephrine may induce unfavorable changes in gene expression of cardiomyocyte. Thus, we investigated effects of epinephrine exposure on the mediation or modulation of gene expression of cultured cardiomyocytes at a genome-wide scale. Our investigation revealed that exposure of cardiomyocytes to epinephrine in an in vitro environment can up-regulate the expression ofangiopoietin-2 gene （~ 2.1 times）, and down-regulate the gene expression of neuregulin 1 （-3.7 times）, plasminogen activator inhibitor-1 （-2.4 times） and SPARC-related modular calcium-binding protein-2 （-4.5 times）. These changes suggest that epinephrine exposure may induce inhibition of angiogenesis-related gene expressions in cultured rat cardiomyocytes. The precise clinical significance of these changes in gene expression, which was induced by epinephrine exposure, warrants further experimental and clinical investigations.

Endoclips vs large or small-volume epinephrine in peptic ulcer recurrent bleeding

AIM:To compare the recurrent bleeding after endoscopic injection of different epinephrine volumes with hemoclips in patients with bleeding peptic ulcer.METHODS:Between January 2005 and December 2009,150 patients with gastric or duodenal bleeding ulcer with major stigmata of hemorrhage and nonbleeding visible vessel in an ulcer bed(Forrest Ⅱa) were included in the study.Patients were randomized to receive a small-volume epinephrine group(15 to 25 mL injection group;Group 1,n = 50),a large-volume epinephrine group(30 to 40 mL injection group;Group 2,n = 50) and a hemoclip group(Group 3,n = 50).The rate of recurrent bleeding,as the primary outcome,was compared between the groups of patients included in the study.Secondary outcomes compared between the groups were primary hemostasis rate,permanent hemostasis,need for emergency surgery,30 d mortality,bleeding-related deaths,length of hospital stay and transfusion requirements.RESULTS:Initial hemostasis was obtained in all patients.The rate of early recurrent bleeding was 30%(15/50) in the small-volume epinephrine group(Group 1) and 16%(8/50) in the large-volume epinephrine group(Group 2)(P = 0.09).The rate of recurrent bleeding was 4%(2/50) in the hemoclip group(Group 3);the difference was statistically significant with regard to patients treated with either small-volume or large-volume epinephrine solution(P = 0.0005 and P = 0.045,respectively).Duration of hospital stay was significantly shorter among patients treated with hemoclips than among patients treated with epinephrine whereas there were no differences in transfusion requirement or even 30 d mortality between the groups.CONCLUSION:Endoclip is superior to both small and large volume injection of epinephrine in the prevention of recurrent bleeding in patients with peptic ulcer.

Epinephrine in out-of-hospital cardiac arrest:A critical review

BACKGROUND： Epinephrine is recommended in advanced cardiac life support guidelines for use in adult cardiac arrest, and has been used in cardiopulmonary resuscitation since 1896. Yet, despite its long time use and incorporation into guidelines, epinephrine suffers from a paucity of evidence regarding its influence on survival. This critical review was conducted to address the knowledge deficit regarding epinephrine in out-of-hospital cardiac arrest and its effect on return of spontaneous circulation, survival to hospital discharge, and neurological performance. METHODS： The EMBASE and MEDLINE （through the Pubmed interface） databases, and the Cochrane library were searched with the key words ＂epinephrine＂, ＂cardiac arrest＂ and variations of these terms. Original research studies concerning epinephrine use in adult, out-of-hospital cardiac arrest were selected for further review. RESULTS： The search yielded nine eligible studies based on inclusion criteria. This includes five prospective cohort studies, one retrospective cohort study, one survival analysis, one case control study, and one RCT. The evidence clearly establishes an association between epinephrine and increased return of spontaneous circulation, the data were conflicting concerning survival to hospital discharge and neurological outcome. CONCLUSIONS： The results of this review exhibit the paucity of evidence regarding the use of epinephrine in out of hospital cardiac arrest. There is currently insufficient evidence to support or reject its administration during resuscitation. Larger sample, placebo controlled, double blind, randomized control trials need to be performed to definitively establish the effect of epinephrine on both survival to hospital discharge and the neurological outcomes of treated patients.

AngiotensinⅡor epinephrine hemodynamic and metabolic responses in the liver of L-NAME induced hypertension and spontaneous hypertensive rats

AIM To study hepatic vasoconstriction and glucose release induced by angiotensin(Ang)Ⅱ or Epi in rats with pharmacological hypertension and spontaneously hypertensive rat(SHR).METHODS Isolated liver perfusion was performed following portal vein and vena cava cannulation; AngⅡ or epinephrine(Epi) was injected in bolus and portal pressure monitored; glucose release was measured in perfusate aliquots. RESULTS The portal hypertensive response(PHR) and the glucose release induced by AngⅡ of L-NAME were similar to normal rats(WIS). On the other hand, the PHR inducedby Epi in L-NAME was higher whereas the glucose release was lower compared to WIS. Despite the similar glycogen content, glucose release induced by AngⅡ was lower in SHR compared to Wistar-Kyoto rats although both PHR and glucose release induced by Epi in were similar. CONCLUSION AngⅡ and Epi responses are altered in different ways in these hypertension models. Our results suggest that inhibition of NO production seems to be involved in the hepatic effects induced by Epi but not by AngⅡ; the diminished glucose release induced by AngⅡ in SHR is not related to glycogen content.